Mechanisms of pronounced and sustained microvascular vasoconstriction during cryotherapy

Cryotherapy is the commonly used application of a cold compress to alleviate pain and swelling with injuries. However, while being one of the more well-known and commonly used therapies, there is limited systematic data collected in controlled environments showing benefits of cryotherapy. Many claims and perceived benefits of cryotherapy are based on empirical and anecdotal evidence, leaving much to be discovered. A typical cryotherapy protocol of 30 minutes can suppress blood flow, tissue temperature, and present with sustained vasoconstriction in the hours after treatment. This vasoconstriction can cause tissue death and necrosis, deemed non-freezing cold injuries, and results in roughly ~1,500 reported clinical cases per year in the United States. Furthermore, non-freezing cold injuries in the civilian population are a rare occurrence, but this type of injury, which relates to these investigations can reach epidemic proportions during times of war. Our primary findings from the research have implicated Rho kinase as being primarily involved in the formation of sustained vasoconstriction following cryotherapy treatment. Additionally, Rho kinase action impairs the temperature blood flow relationship that is necessary for abolishing much of the risk of ischemic injury. Secondary findings have furthered our knowledge of mechanisms of locally induced vasoconstriction and the significance of the sympathetic nerves in returning blood flow towards basal conditions following cryotherapy treatment. Finally, these investigations have shown that there appears to be limited involvement of nitric oxide in the lower ranges of blood flow. This finding might suggest that during a pronounced vasoconstrictive state (60-80% reduction in basal blood flow) much of the action of Rho kinase drives its activity by enhancing adrenergic activity. Our findings are generally in agreement with previous literature investigating mechanisms of cold-induced vasoconstriction. However, these previous studies typically made measurements on much smaller skin surfaces and also used much more mild temperatures for cooling. Accordingly, these findings outlined in the current studies improve our understanding of the vascular kinetics of cryotherapy use. We conclude that there needs to be a greater understanding and awareness provided to layman users of cryotherapy, allowing them to understand the risks and appropriate methods of application.